PROJECT SUMMARY - BIOLOGY OF COLON CANCER PROGRAM Research in the Biology of Colon Cancer (BCC) program is focused on basic aspects of the biology of colorectal cancer, encompassing how genetic and dietary factors contribute to normal mucosal homeostasis, the perturbations that alter probability of tumorigenesis and its progression, and how this knowledge can be exploited to identify new approaches for the prevention, progression and treatment of this disease. Over the last several years research has increasingly focused on the role of intestinal stem cells in the development, progression and refractoriness of this disease, capitalizing on the program's development of novel genetic and environmentally-driven mouse models for these studies. As a disease of aging, there is also a focus on aging- associated changes in mucosal and stem cell functions, in particular genetic and epigenetic alterations, and in autophagic processes that are risk factors for colorectal cancer. New studies have focused on the role of the microbiome in the development of intestinal inflammation, a precursor of colorectal cancer, and the impact of the bacterial flora on the catabolism of antineoplastic agents to toxic derivatives. There has also been an increased emphasis on translational research, especially in addressing the underserved minority populations that comprise the AECC catchment area, the Bronx. While several BCC members moved on from Einstein over the last two funding cycles, the program has recruited key new members in specifically targeted areas to address the intestinal microbiome, epigenetic regulation, and to extend screening and genetic testing to the Bronx population, thereby expanding the scope of the program. Also new to the program is the recruitment of Lawrence Brandt as co-leader who brings expertise in inflammatory disease and fecal transplantation to reinforce and expand the translational aspects of BCC research. There are three thematic aims of the program: (i) To Identify Environmental, Genetic and the Niche Impact on Intestinal Stem Cell Functions in Homeostasis and Tumorigenesis, (ii) To investigate aging as a Risk Factor for Intestinal Tumors, and (iii) To address prevention and therapy: Genetics, Modulation and Translation. There are 20 program members from 11 departments. Current NCI funding is 2.4M (dc); total peer-reviewed funding is $4.9M (dc). There were 460 publications since July 2013 of which 11% represented intra-programmatic, 23% inter-programmatic and 58% represent collaborations with investigators at other institutions.